br Patients were tested by
Patients were tested by appropriate routine diagnostic pro-cesses to detect any mutation in highly penetrant genes, namely, BRCA1 or BRCA2 cancer predisposition CH 223191 routinely from 2009
Please cite this article as: Szollar A et al., A long-term retrospective comparative study of the oncological outcomes of 598 very young ( 35 years) and young (36e45 years) breast cancer patients, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2019.06.007
A. Szollar et al. / European Journal of Surgical Oncology xxx (xxxx) xxx 3
according to the ESMO recommendation . The current study was approved by the Institutional Review Board at the NIO. Informed consent was obtained from all patients. Germline DNA was extracted by a standard procedure from the blood of patients diagnosed with breast cancer at the NIO. In Hungary, genetic testing for the presence of germline mutations of BRCA1/2 genes has been conducted at the Department of Molecular Genetics, National Institute of Oncology since 1995 [30e32]. Sanger sequencing (1995-present), denaturing high-performance liquid chromatography (DHPLC) (2004e2012), and multiplex ligation-dependent probe amplification (MLPA) (2004-present) were the molecular diagnostic methods used. From 1995 to 2004 samples were pre-screened by heteroduplex analysis (HDA) or Single-Strand Conformation Poly-morphism (SSCP) analysis, but mutations were identified by Sanger sequencing or MLPA. From 2013 onward, next-generation sequencing (NGS) is performed on a MiSeq instrument (Illumina Inc., San Diego, CA) using the platform-installed MiSeq Reporter's workflow. Women were offered testing if their family and personal history fulfilled the selection criteria of Breast Cancer Linkage Consortium or NCCN Clinical Practice Guidelines for Genetic/Fa-milial High-Risk Assessment [30e32]. .
During the investigated period and according to the updated international European Society of Medical Oncology (ESMO) Clin-ical Practice Guidelines for diagnosis, treatment and follow-up, the chemotherapy regimen was based on FAC (5-fluorouracil, doxoru-bicin, and cyclophosphamide), FEC (5-fluorouracil, epirubicin, and cyclophosphamide) and taxanes. Chemotherapy was indicated in triple-negative, HER2-positive breast cancers and in high-risk luminal HER2-negative tumours. Depending on the individual recurrence risk and the selected regimen, chemotherapy was usu-ally administered for six cycles. Endocrine therapy (ET) was based on tamoxifen or aromatase inhibitors with an LHRH agonist in luminal cases for five years after the surgery. After 2005, all HER2-positive patients with pT1c or larger tumours received adjuvant trastuzumab therapy, which was administered once per week during treatment with other chemotherapy medications and then once every 3 weeks after treatment with the other medications for up to 52 weeks. Radiotherapy (RT) was performed using CT-based three-dimensional treatment planning. The adjuvant radiotherapy started 4e8 weeks after surgeryor 3e4 weeks after adjuvant chemotherapy. Patients who received BCS were given whole breast radiotherapy and tumour bed boost irradiation. Postmastectomy radiotherapy (PMRT) to the chest wall was administered to patients with pT3eT4 pN0-1mi tumours. Locoregional PMRT was indicated for patients with lymph node metastatases >2 mm (pN1a, pN2a, pN3a). Doses used for local and/or regional adjuvant irradiation were 50 Gy in 25 fractions of 2.0 Gy with a typical boost dose of 16 Gy in 2 Gy single doses.
Medical records and pathology reports were reviewed, and in-formation on the HER2, ER and PR status of the patients, as well as data on the age at diagnosis, histological grade, stage, and other clinical covariates, was collected from the institutional database retrospectively. The TNM classification was defined by the Amer-ican Joint Cancer Committee (AJCC) and the Union for International Cancer Control (UICC) Breast Cancer Staging 7th Edition .